This research project is aimed at the characterization of feline Gm2 gangliosidosis and at its utilization as an animal model for devising therapeutic methodologies based on enzyme replacement, of possible aplication to human patients witn Gm2 gangliosidosis. The specific aims of the research are: Biochemical and immunological characterization of normal feline Beta-hexosaminidase. 2) Characterization of the enzymatic defect in affected animals to establish homologies with the human disease. 3) Study of organ disposition and uptake mechanisms, stability and activity of human Beta-hexosaminidase injected into normal cats. 4) Study of methods for the induction of temporary blood-brain barrier permeability to exogenous enzyme. 5) Applicationof techniques developed in 3) and 4) to affected animas; and evaluation of their effect on glycolipid storage. Rattazzi, M.C., McCullough, R.A., Downing, C., and Kung, M.P.: Toward enzyme therapy in Gm2 gangliosidosis: Beta-hexosaminidase infusion in normal cas. Ped. Res. 13:916, 1979. Vladutiu, G.D., and Rattazzi, M.C.: The excretion-reuptake route of Beta-hexosaminidase in normal and I-cell disease cultured fibroblasts. J. Clin. Invest. 63:595, 1979.